AB0743 Biomarkers in systemic sclerosis: a 23-plex cytokine/chemokine analysis
Authors: C. Perricone, G. Cafaro, R. Ilenia, S. Calvacchi, E. Marcucci, S. Cipriani, O. Bistoni, R. Gerli, E. Bartoloni Bocci
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic Sclerosis (SSc) is a rare inflammatory disease of unknown etiology associated with multi-organ involvement. Biomarkers remain urgently needed as tools for differential diagnosis, prognosis, disease progression, and as therapeutic response predictors in SSc. Ideally, for widespread utility, biomarkers should be easy to sample and analyse. Objectives We aimed at evaluating potentially pathogenic circulating key cytokines/chemokines in a monocentric cohort of SSc patients. Methods Sera were drawn from SSc patients and 23 cytokines/chemokines (CCL2/MCP-1, IP-10/CXCL10, Flt3 Ligand, IFNa2, IL6, IL7, IL12, IL13, IL15, IL17A, TNFa, IL-1Ra, CXCL13, IL21, IL23, IL33, TSLP, IL-2RA, IL1RII, TNFRII, BAFF, CCL19/MIP-3B 66, MMP-8) were quantified using Luminex multiplex immunoassay (BioRad-BioPlex 200 System-Lumine x-Map technology R&amp;D Systems, USA) following the manufacturer’s instructions and customized procedures. Data were acquired using Bioplex manager v 6.1. P value ≤ 0.05 was considered to be significant. Data were analyzed using GraphPad Prism V.8 (GraphPad Software, Inc.) software. Results Clinical and demographic features of 17 SSc (5 dcSSc, 12 lcSSc) patients are reported in Table 1. Mean±SD age was 55±14.68 years, mean±SD disease duration was 89.47±95.34 months. We found that MCP-1 levels inversely correlated with PAPs (r=-0.55, P=0.03) and IP10 with anti-Scl70 (r=-0.561, P=0.004), Figure 1. No other associations were found Table 1. N % Sex 2M/15F 11.8/88.32 Age (years, mean±SD) 55±14.68 Disease duration (months, mean±SD) 89.47±95.34 Cigarette smoke 8 47 Raynaud’s phenomenon 17 100 Skin thickening 14 82.4 Ulcers 2 11.8 Rodnan’s Skin Score (mean±SD) 5.9±6.6 Articular involvement 2 11.8 Heart involvement 0 0 Paps max (mmhg, mean±SD) 28.3±5.9 Pulmonary involvement 5 29.4 DLCO min (%, mean±SD) 90.24±21.2 Gastrointestinal involvement 3 17.6 ANA 17 100 Rheumatoid factor 4 23.5 Anti-Scl70 (U/ml, mean±SD) 33.2±59.3 Anti-CENP(U/ml, mean±SD) 55.9±48.9 Anti-SSA 2 11.8 Anti-SSB 1 5.9 Anti-Sm 1 5.9 Anti-RNP 1 5.9 Elevated Blood Pressure 4 23.5 Obesity 1 5.8 Any DMARD 5 29.4 Conclusion We confirm a potential pathogenic role for MCP-1 in SSc. The -2518 promotor polymorphism in the MCP-1 gene has been already associated with disease susceptibility and an increased expression of the molecule both in peripheral blood and in the skin has been described. Intriguingly, MCP-1 seems to drive skin fibrosis while the role played in pulmonary involvement is more controversial. Indeed, similarly to our results, Scala et al. found an inverse correlation between pulmonary fibrosis and MCP-1 from T cell lines (1). At the same extent, the observation that IP-10 has an inverse correlation with anti-Scl70 levels is not novel and the usage of this chemokine as a marker of lcSSc has been already suggested. In this view, Zhu et al. found that Scl-70 negative patients have a higher expression of IP-10 than Scl-70 positive (1,878 (2,964) ng/L vs 1,030 (2,196.6) ng/L, P&lt;0.05) (2). Finally, this is the first report on MMP8 in SSc and we suggest that MMP8 - a collagenase and marker of idiopathic pulmonary fibrosis involved in the migration of fibroblasts - can represent a promising biomarker for SSc diagnosis. References [1]Scala et al. Clin Exp Immunol 2004 [2]Beijing Da Xue Xue Bao Yi Xue Ban. 2019 Figure 1. Disclosure of Interests None declared